Rhodiola rosea is a popular medicinal plant that is commonly used as an adaptogen in folklore medicine in Europe and Asia due to its ability to increase an organism's resistance to physical, chemical and biological stress. The aim of this study was to determine the central nervous system activity and toxicity parameters of R. rosea. An ethanol extract from the roots of R. rosea was orally (p.o.) administered to mice (10–316 mg/kg); exploratory activity, anti-anxiety, behavior, sodium pentobarbital-induced hypnosis, antinociceptive effects, and pentylenetetrazole-induced seizures were tested. The results from the experimental models tested showed a significant reduction in exploratory behavior and in the number of rearings and head dippings, but no change in the sedative-hypnotic and anticonvulsant response with respect to vehicle. Moreover, R. rosea reduced the licking time in the formalin test. R. rosea was not toxic in Artemia salina and in mice. The present results confirm some preclinical and clinical studies that indicate stimulating, anxiolytic-like effects and present new evidence of the antinociceptive effect of and very low risk of toxicity from R. rosea.